Recent studies have demonstrated that thyroxine and triiodothyronine are highly localized in synaptosomal fractions of brain. A number of psychotropic drug effects are known to be enhanced by treatment with thyroid hormones. Since these hormones produce marked effects on behavior, actions of iodothyronines and of psychotropic drugs may intersect at the synapse. Although there is no request for support of clinical studies at the present time, the proposed animal research is designed to provide information directly applicable to problems in clinical psychiatry. The immediate aims of the investigations are: (1) To determine the psychobiologic implications of synaptosomally localized iodothyronines; (2) To evaluate the effects of psychotropic drugs on the function, kinetics and molecular forms of iodothyronines in nerve endings; (3) To provide and test specified psychopharmacologic agents derived from iodothyronines for their potential usefulness in the treatment of mental illness. Interactions of thyroid hormones and drugs will be studied by means of autoradiographic, immunofluorescence, neurochemical and neurobiologic procedures.